Biology subjects

Zhuang, W.

Publications and source records attributed to Zhuang, W..

6 recordsLinked to original sources

bioRxiv2025

SMART: an approach for accurate formula assignment in spatially-resolved metabolomics

Spatially-resolved metabolomics plays a critical role in unraveling tissue-specific metabolic complexities. Despite its significance, this profound technology generates thousands of features, yet accurate annotation significantly lags behind LC-MS-based approaches. To bridge this gap, we introduce SMART, an open-source platform designed for precise formula assignment in mass spectrometry imaging. SMART constructs a KnownSet database containing 2.8 million formulas linked by DBEdges derived from repositories such as HMDB, ChEMBL, PubChem, and BioEdges from KEGG biological reactant pairs. Using a multiple linear regression model, SMART extracts formula networks associated with the m/z of interest and scores potential candidates based on several criteria, including linked formulas, DBEdges/BioEdges, and ppm values. Benchmarking against reference datasets demonstrates that SMART achieves prediction accuracy rates of up to 92.4%. Applied to mass spectrometry imaging, SMART successfully annotated 986 formulas in developing mouse embryos. This robust platform enables systematic formula annotation within tissues, enhancing our understanding of metabolic heterogeneity.

bioinformatics↗

bioRxiv2024

The sodium-glucose cotransporter 2 inhibitor tofogliflozin induces vasodilation by activating Kv channels, the SERCA pump, and the sGC/cGMP pathway

OBJECTIVETofogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor widely used to treat T2DM, but it also exhibits cardio-protective effects. This study investigated the vasodilatory action of tofogliflozin using rabbit femoral artery rings pre-contracted with phenylephrine. APPROACH AND RESULTSThe femoral artery quickly separated from the rabbit and fix it to the organ bath chamber. Subsequently, administer an inhibitor that modulates vascular tension in the rings or remove the endothelium to assess its impact on vasodilation. The results showed the concentration-dependent induction of vasodilation by tofogliflozin, a response that remained unchanged following endothelial removal, pretreatment with the nitric oxide synthase (NOS) inhibitor L-NAME, or the inhibition of low- and intermediate-conductance Ca2+-activated K+ channels (SKCa and IKCa) using apamin in combination with TRAM-34. Furthermore, pretreatment with the voltage-dependent K+ (Kv) channel inhibitor 4-AP reduced the vasodilatory effects of tofogliflozin whereas pretreatment with the ATP-sensitive K+ (KATP) channel inhibitor glibenclamide or the large-conductance Ca2+-activated K+ (BKCa) channel inhibitor paxilline did not. Notably, our findings indicated that Kv7.X, rather than Kv1.5 or Kv2.1, is the primary Kv subtype involved in tofogliflozin-induced vasodilation. The vasodilatory effects of tofogliflozin were also significantly inhibited in femoral arterial rings pretreated with the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors thapsigargin and cyclopiazonic acid (CPA). Tofogliflozin-induced vasodilation was unaltered in arterial rings exposed to the adenylyl cyclase inhibitor SQ 22536, the protein kinase A (PKA) inhibitor KT 5720, and the protein kinase G (PKG) inhibitor KT 582 whereas it was effectively reduced by the soluble guanylyl cyclase (sGC) inhibitor ODQ. CONCLUSIONSThese findings suggest that tofogliflozin-induced vasodilation is mediated by the activation of the SERCA pump, the sGC/cGMP pathway, and Kv channels, but not the PKA signaling pathway, other K+ channels, or endothelium-dependent mechanisms.

pharmacology and toxicology↗

bioRxiv2024

Differential seasonal effects of ephemeral legumes in response to moisture-nitrogen coupling in the deserts of northwestern China

Desert ecosystems are ecosystems limited by both nitrogen and moisture, while legumes, as an important source of nitrogen in desert ecosystems, are extremely sensitive to respond to moisture and nitrogen changes. In order to reveal the growth and physiological metabolic processes of desert legumes in response to moisture and nitrogen changes. In this study, two dominant ephemeral legumes, Trigonella arcuata C. A. Mey. and Astragalus arpilobus Kar. & Kir. were selected from the Gurbantunggut Desert through a controlled experiment in greenhouse pots: four moisture treatment levels were established: W1(soil moisture content of 5 %), W2(soil moisture content of 7 %), W3( 9 % soil moisture content), W4(11 % soil moisture content) and three N treatment levels: N1(0 mmol/L 15NH4 15NO3), N2(18 mmol/L 15NH4 15NO3), N3(72 mmol/L 15NH4 15NO3), and we conducted a 15N tracking experiment for the pot treatments throughout the growing season. The results showed that: (1) moisture and nitrogen treatments had similar patterns on above-ground and below-ground as well as total fresh weight, plant height and basal diameter, Chla, Chlb and Chla+b of the two legumes, all of which were greatest in the W3N3 treatment and smallest in the W4N1 treatment, but the growth characteristics and chlorophyll parameters had cumulative differences over the growing season. (2) When subjected to severe moisture and nitrogen stresses, the 2 plants would increase the physiological levels of stress tolerance in vivo to enhance cellular resistance, with the osmoregulatory substance content being the most sensitive in response to moisture, and the cell membrane and antioxidant enzyme systems being the most sensitive in response to nitrogen stress. (3) The adaptive characteristics of physiological metabolic processes in plants to seasonal changes, in which growth characteristics, cell membrane and antioxidant enzyme content accumulation showed: rapid growth period < maximum biomass period, while chlorophyll content and osmoregulatory substance content accumulation content accumulation showed: rapid growth period > maximum biomass period. In general, drought can hinder nitrogen uptake and transport, while sufficient moisture can accelerate the nutrient metabolism process of plants, and there is a nutrient dilution effect once the moisture is in excess, but in the nitrogen starvation state, the moisture factor has almost no effect on plants, therefore, the moisture-nitrogen coupling effect is more reflective of the physiological response characteristics of the plants when they encountered the adversity stress, and the degree of accumulation is different in different growing seasons, and the plants in the The differences in different growing seasons reflect the changes in photosynthetic intensity and energy demand.

ecology↗

bioRxiv2023

Nitrite deteriorates bioreactor performance by reducing growth of Ca. Brocadia sapporoensis instead of inhibiting the anammox activity

Effects of nitrite on anammox activities have been of widespread concern. However, the molecular mechanisms of specific microorganisms in anammox systems responding to nitrite remain unexplored. This study investigated the effects of excess nitrite on core metabolism of AnAOB and symbiotic bacteria, and further elucidated the response mechanism of these effects on microbial growth and nitrogen removal performance. Specifically, nitrogen removal process in a continuous-flow anaerobic ammonia oxidation membrane bioreactor completely collapsed when the nitrite concentration reached 243 mg N/L. Integrated meta-omics analyses demonstrated that excess nitrite disrupted the energy metabolism of Ca. Brocadia sapporoensis (AMXB1), reducing the energy available for establishing tolerance. It disrupted cell replication by impairing biosynthesis process of AMXB1, especially DNA replication and the formation of vital cell structures, e.g., cell membrane and cell wall, as well as the cellular protection system, leading to the collapse of the anammox system. In addition, the cross-feeding of glycogen, lipopolysaccharide and amino acid between AMXB1 and symbiotic bacteria was hindered by excess nitrite, which also contributed to the anomalous cell proliferation and metabolism of AMXB1. These findings contribute to our understanding of the ability of anammox consortia to respond to nitrite stress and process stability in engineered ecosystems. HighlightsO_LINO --N concentration of 243 mg N/L caused the performance collapse of a continuous-flow anammox MBR. C_LIO_LIExcess nitrite likely disrupted the energy metabolism of AMXB1, reducing the energy availability for mitigating nitrite toxicity. C_LIO_LIThe cross-feeding between AMXB1 and symbiotic bacteria was hindered by excess nitrite. C_LIO_LIThe hindrance of cross-feeding was reversed as the concentration of nitrite decreased. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/568540v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@6b199forg.highwire.dtl.DTLVardef@15f2a74org.highwire.dtl.DTLVardef@dc2d8eorg.highwire.dtl.DTLVardef@132deb1_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2021

Recovery of high-qualitied Genomes from a deep-inland Salt Lake Using BASALT

Metagenomic binning enables the in-depth characterization of microorganisms. To improve the resolution and efficiency of metagenomic binning, BASALT (Binning Across a Series of AssembLies Toolkit), a novel binning toolkit was present in this study, which recovers, compares and optimizes metagenomic assembled genomes (MAGs) across a series of assemblies from short-read, long-read or hybrid strategies. BASALT incorporates self-designed algorithms which automates the separation of redundant bins, elongate and refine best bins and improve contiguity. Evaluation using mock communities revealed that BASALT auto-binning obtained up to 51% more number of MAGs with up to 10 times better MAG quality from microbial community at low (132 genomes) and medium (596 genomes) complexity, compared to other binners such as DASTool, VAMB and metaWRAP. Using BASALT, a case-study analysis of a Salt Lake sediment microbial community from northwest arid region of China was performed, resulting in 426 non-redundant MAGs, including 352 and 69 bacterial and archaeal MAGs which could not be assigned to any known species from GTDB (ANI < 95%), respectively. In addition, two Lokiarchaeotal MAGs that belong to superphylum Asgardarchaeota were observed from Salt Lake sediment samples. This is the first time that candidate species from phylum Lokiarchaeota was found in the arid and deep-inland environment, filling the current knowledge gap of earth microbiome. Overall, BASALT is proven to be a robust toolkit for metagenomic binning, and more importantly, expand the Tree of Life.

bioinformatics↗

bioRxiv2020

MEKK3-MEK5-ERK5 signaling promotes mitochondrial degradation

Mitochondria are vital organelles that coordinate cellular energy homeostasis and have important roles in cell death. Therefore, the removal of damaged or excessive mitochondria is critical for maintaining proper cellular function. The PINK1-Parkin pathway removes acutely damaged mitochondria through a well-characterized mitophagy pathway, but basal mitochondrial turnover occurs via distinct and less well-understood mechanisms. Here we report that the MEKK3-MEK5-ERK5 kinase cascade is required for mitochondrial degradation in the absence of exogenous damage. We demonstrate that genetic or pharmacological inhibition of the MEKK3-MEK5-ERK5 pathway increases mitochondrial content by reducing lysosome-mediated degradation of mitochondria under basal conditions. We show that the MEKK3-MEK5-ERK5 pathway plays a selective role in basal mitochondrial degradation but is not required for non-selective bulk autophagy, damage-induced mitophagy, or restraint of mitochondrial biogenesis. This illuminates the MEKK3-MEK5-ERK5 pathway as a positive regulator of mitochondrial degradation that acts independently of exogenous mitochondrial stressors.

cell biology↗